The incidence of PALB2 c.3113G>A in women with a strong family history of breast and ovarian cancer attending familial cancer centres in Australia

Fam Cancer. 2013 Dec;12(4):587-95. doi: 10.1007/s10689-013-9620-4.

Abstract

The familial aggregation of breast cancer has been well-described with approximately 25% of breast cancers attributable to inherited mutations in currently known breast cancer susceptibility genes. PALB2 c.3113G>A (p.Trp1038*) is a protein-truncating mutation which has been associated with high estimated risk of breast cancer in Australian women (91%; 95% CI = 44-100) to age 70 years. This study screened for PALB2 c.3113G>A in germline DNA representing 871 unrelated individuals from "high-risk" breast and/or ovarian cancer families evaluated in the setting of a Familial Cancer Centre in Australia. The PALB2 c.3113G>A mutation was identified in eight of 871 probands (0.92%) from these families. Median age of diagnosis was 42 years. Five of these eight women had contra-lateral breast cancers. Available data suggests that PALB2 c.3113G>A is a rare mutation with estimated breast cancer risks similar in magnitude to that associated with BRCA2 mutations. Although the proportion of high-risk women carrying this PALB2 mutation is low, research efforts should continue in order to effect its translation into clinical genetic testing practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Australia / epidemiology
  • Breast Neoplasms / genetics*
  • Cancer Care Facilities
  • DNA, Neoplasm / genetics
  • Fanconi Anemia Complementation Group N Protein
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Humans
  • Incidence
  • Middle Aged
  • Mutation / genetics*
  • Nuclear Proteins / genetics*
  • Ovarian Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Prognosis
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • DNA, Neoplasm
  • Fanconi Anemia Complementation Group N Protein
  • Nuclear Proteins
  • PALB2 protein, human
  • Tumor Suppressor Proteins